Establishment and characterization of a canine soft tissue sarcoma patient-derived xenograft model.

Spontaneously occurring soft tissue sarcoma (STS) is relatively common in canine cancer patients. Because of the similarities to human disease, canine STSs are a valuable and readily available resource for the study of new therapeutics. In this study, a canine patient-derived xenograft (PDX) model, CDX-STS2, was established. The CDX-STS2 model was engrafted and expanded for systemic administration studies with chemotherapeutic agents commonly used to treat STS, including doxorubicin, docetaxel and gemcitabine. Immunohistochemistry for drug-specific biomarkers and tumour growth measurement revealed tumour sensitivity to doxorubicin and docetaxel, whereas gemcitabine had no effect on tumour growth. Although many human PDX tumour models have been established, relatively few canine PDX models have been reported to date. CDX-STS2 represents a new STS PDX research model of canine origin that will be useful in bridging preclinical research with clinical studies of STS in pet dogs.

Placing an upper limit on cryptic marine sulphur cycling.

A quantitative understanding of sources and sinks of fixed nitrogen in low-oxygen waters is required to explain the role of oxygen-minimum zones (OMZs) in controlling the fixed nitrogen inventory of the global ocean. Apparent imbalances in geochemical nitrogen budgets have spurred numerous studies to measure the contributions of heterotrophic and autotrophic N2-producing metabolisms (denitrification and anaerobic ammonia oxidation, respectively). Recently, 'cryptic' sulphur cycling was proposed as a partial solution to the fundamental biogeochemical problem of closing marine fixed-nitrogen budgets in intensely oxygen-deficient regions. The degree to which the cryptic sulphur cycle can fuel a loss of fixed nitrogen in the modern ocean requires the quantification of sulphur recycling in OMZ settings. Here we provide a new constraint for OMZ sulphate reduction based on isotopic profiles of oxygen ((18)O/(16)O) and sulphur ((33)S/(32)S, (34)S/(32)S) in seawater sulphate through oxygenated open-ocean and OMZ-bearing water columns. When coupled with observations and models of sulphate isotope dynamics and data-constrained model estimates of OMZ water-mass residence time, we find that previous estimates for sulphur-driven remineralization and loss of fixed nitrogen from the oceans are near the upper limit for what is possible given in situ sulphate isotope data.

Effect of glucagon on hepatic phenylalanine hydroxylase in vivo.

Moderate doses of glucagon (20 micrograms/kg I.V.) are sufficient to stimulate rat hepatic phenylalanine hydroxylase in vivo. In addition, the stimulation of the tetrahydrobiopterin-dependent phenylalanine hydroxylase activity in livers of animals fed on a high-protein diet has been correlated with an elevated phosphate content. The tetrahydrobiopterin-dependent hydroxylase activity in these animals can be further elevated by glucagon-stimulated phosphorylation. These results indicate that physiological changes in glucagon concentration modulate rat liver phenylalanine hydroxylase activity in vivo. The current understanding of the role of phosphorylation in regulating human phenylalanine hydroxylase is also considered.